1. Field of the Invention
The present invention relates to a porous ceramics body for in vivo and in vitro use and more particularly to a porous ceramics body for in vivo use made of a calcium phosphate sintered material which is preferably used for artificial bones and as a filling material for such artificial bones and has an excellent property in forming osseous tissues of a living body as well as a high degree of strength and also to a culture vessel for cells.
2. Description of the Related Art
In the medical fields such as surgery or orthopaedic surgery, the reconstruction of osseous tissues of a patient having defective portions or cavities in his or her bones caused by a disease, an accident or an surgical operation was conventionally practiced by collecting osseous materials from another portion of the patient""s own body or the body of his or her parent, relatives, brothers or sisters to fill such defective portions or cavities.
However, a surgical operation for collecting such osseous materials is accompanied by unbearable pains in addition to requiring tremendous expenses and labor. Further, there is a limitation in filling the defective portions with human osseous materials alone and, if the defective portions in the patient""s body covers an extensive area, it is very often impossible to secure a sufficient amount of human osseous materials.
Recently, therefore, the research work on artificial filling material for bones came to be strenuously conducted.
In this connection, it is needed in burying artificial osseous materials that such artificial osseous materials are nontoxic and safe as well as having a high degree of mechanical strength and affinity with living tissues such that said artificial osseous materials easily become integrated with osseous tissue cells and vessel systems. Such material so far proposed includes sintered calcium phosphates such as tricalcium phosphate, hydroxy apatite or the like.
However, there is a problem that osseous tissues in a living body are not formed quickly if a sintered nonporous (or solid) member of calcium phosphate is buried therein with the result that an extremely long time is needed for recovery.
Therefore, it is proposed to provide a sintered porous body of calcium phosphate which is to be buried in a living body to assure a quick integration with a living tissues after actually buried; that is, there is proposed a sintered porous body of calcium phosphate which allows easy entry of osseous tissues.
The thus proposed conventional sintered porous body of calcium phosphate is formed of immature sintered porous material having an innumerable number of fine open pores in the walls portions. Here, the reference to the immature sintered porous body was made to clarify that the crystalline particles to form a sintered body are not sufficiently connected, thus leaving gaps therebetween with the result that a number of fine pores having diameters substantially smaller than those of the crystalline particles are dispersed all over the sintered body.
With the immature sintered porous body having an innumerable number of fine pores in the walls portions (the diameters of the majority of said pores are as small as to the order of microns (xcexcm) or less), it was conventionally thought that formation of bones are actively done by virtue of such fine pores.
Now back to the proposed conventional porous ceramics body for in vivo use (sintered porous body of calcium phosphate), there is a problem that said body cannot be used for treatment of large defective portions in a bone because sufficient mechanical strength as required for an artificial bone is not attained as the immature sintered porous body has an innumerable number of fine open pores in the wall portions.
On the other hand, there is another problem that an extremely long period of time is needed for recovery of the patient because osseous tissues in a living body are not quickly formed if a solid sintered body of calcium phosphate is used for the ceramics body for in vivo use in order to assure the mechanical strength as mentioned above.
The inventors made an intensive research work in order to overcome the above shortcomings of the conventional porous ceramics body for in vivo use (a sintered body of calcium phosphate). As a result, the reduction of strength in the sintered body of calcium phosphate was found less if said ceramics body of calcium phosphate has a particular pore structure, thus retaining the strength required for artificial bones and artificial osseous filling material. Further, it was found that said particular pore structure of the sintered calcium phosphate body assures quick formation of osseous tissues as a result of osseous tissue cells (osteoblast cells) and blood vessels entering the pores such that formation of the osseous tissues is prompted. Based on this knowledge, the inventors have completed the porous ceramics body for in vivo or in vitro use according to the present invention.
The present invention has been made to solve the problems discussed hereinbefore and its object is to provide a porous ceramics body for in vivo or in vitro use which is excellent in maintaining a sufficient mechanical strength while prompting the formation of osseous system tissues such that suitable artificial bones, an artificial filling material for osseous systems.
The porous ceramics body according to the present invention is characterized in that a number of pores are closely distributed in three dimensional directions, adjoining pores thereof being partitioned by wall portions formed with respective communication ports to bring said adjoining pores into communication with each other such that a vacancy of a series of spherical pores are formed therewithin, said porous ceramics body being made of a sintered calcium phosphate body, characterized in that, within said sintered calcium phosphate body, pores each having a diameter of 5 microns (xcexcm) or more account for 80% or more of all the pores in terms of volume whereas pores having a diameter of less than 5 microns (xcexcm) account for less than 20% of all the pores in terms of volume as subjected to a mercury porosimeter measurement.
As disclosed hereinbefore, the porous ceramics body according to the present invention is characterized in that a series of spherical pores are closely distributed in three dimensional directions such that said series of spherical pores allow the entry of osseous system cells (osteoblast cells) thereinto through the communication ports whereas adjoining pores are partitioned by wall portions in which there are substantially no open pores having a diameter of less than 5 microns (xcexcm), said porous ceramics body being made of a sintered calcium phosphate body.
That is, the porous ceramics body for in vivo use according to the present invention is made of the sintered calcium phosphate body of the aforementioned structure having therein a number of open pores to allow the entry of osseous system cells (osteoblast cells or the like) and blood vessels thereinto whereas there are substantially no pores except the communication ports in the wall portions.
Further, it is preferable that the volume of the pores having a diameter of 5 microns (xcexcm) or more accounts for 90% of all the pores or more and the ratio of 93% or more is further preferable.
Therefore, it is easy for osseous system cells (osteoblast cells or the like) to enter the porous body, thus prompting the formation of osseous systems. Further, the substantial absence of pores in the wall portions prevents remarkable reduction in the mechanical strength as compared with a solid sintered calcium phosphate body with the result that a predetermined mechanical strength required for artificial bones is assured.
In this connection, it is to be noted that it is achieved by complete sintering to minimize fine pores in the wall portions which partition adjoining pores like in the porous ceramics body according to the present invention. The complete sintering means in this context that crystalline particles constituting the sintered body are completely connected to each other leaving no gaps therebetween to such an extent that there are substantially no pores smaller than the crystalline particles all through the sintered body.
Further, it was observed that osseous systems are sufficiently formed in the completely sintered body like in the porous ceramics body according to the present invention and that the porous ceramics body according to the present invention is suitable for artificial bones and a filling material for artificial osseous systems.
It is preferable here that pores accounting for an accumulated ratio of 50% in terms of volume have a diameter of 10 to 600 microns (xcexcm) as subjected to a mercury porosimeter measurement.
In this way, since pores accounting for an accumulated ratio of 50% in terms of volume have a diameter in the range of 10 to 600 microns (xcexcm) as subjected to a mercury porosimeter measurement, osseous system cells (osteoblast cells or the like) are quickly admitted into the porous ceramics body for in vivo or in vitro use to prompt the formation of osseous systems.
It is to be noted that it is impossible to effectively admit osseous system cells (osteoblast cells or the like) into the porous ceramics body for in vivo or in vitro use if pores accounting for an accumulated ratio of 50% in terms of volume have a diameter less than 10 microns (xcexcm). If, on the other hand, pores accounting for an accumulated ratio of 50% in terms of volume have a diameter more than 600 microns (xcexcm), osseous system cells (osteoblast cells or the like) which have been admitted thereinto will flow out without making the formation of osseous systems. Therefore, it is preferable that pores accounting for an accumulated ratio of 50% in terms of volume have a diameter of 10 to 600 microns (xcexcm) as subjected to a mercury porosimeter measurement.
It is further preferable that pores accounting for an accumulated ration of 50% in terms of volume have a diameter of 20 to 200 microns (xcexcm) if the mechanical strength thereof and the cell entry and subsequent stability thereat is to be considered and, in this respect, the diameter of 30 to 100 microns (xcexcm) is still further preferable.
It is still further preferable that said sintered calcium phosphate body has a porosity of 45 to 90%.
If the porosity is less than 45%, the distribution of the pores is too sparse to obtain a series of spherical pores in mutual communication. A porous ceramics body which does not have a series of spherical pores in mutual communication has a problem that osseous system cells (osteoblast cells or the like) will not be admitted thereinto.
Further, if the porosity of the sintered calcium phosphate body is more than 90%, the mechanical strength of the porous ceramics body falls to such an extent the same is not suitable for artificial bones.
Therefore, it is preferable that said sintered calcium phosphate body has a porosity of 45 to 90%.
It is further preferable that said sintered calcium phosphate body is a sintered body made of a material selected from hydroxy apatite, tricalcium phosphate and a composite material thereof. Hydroxy apatite is particularly preferable.
Such sintered calcium phosphate body adopted for the porous ceramics body for in vivo use has an affinity with the human body and converted into complete osseous systems. Therefore, the need for a re-operation to remove surgical titanium or stainless steel members is eliminated.
It is further preferable that each wall portion has a surface spread with calcium phosphate particles closely as if stone pavement, given calcium phosphate particles cooperating to define a recess therebetween, said recess having a diameter equal to or less than a mean particle diameter.
Due to the structure as disclosed above, cells take root uniformly and extensively. Further, the particles hardly fall off from the surface of the wall portions of the porous ceramics body such that there is no cause for cracks to be formed, thus improving the strength thereof. Further, calcium phosphate particles are securely joined to each other to prevent them from falling off therefrom such that washing thereof is easily done.
In this connection, the disclosure to the effect that given calcium phosphate particles cooperate to define a recess therebetween and that said recess has diameter equal to or less than a mean particle diameter means that the height h shown in FIG. 15 is equal to or less than a mean particle diameter. Such calcium phosphate particles and those therearound make a flat surface, thus providing an extensive contact area between the particles which prevents a possibility to drop therefrom and contributes to improvement of strength. If there is cutting dust on the surface, it can be difficult for fluid to enter the sintered calcium phosphate body. The sintered calcium phosphate body according to the present invention controls generation of floating particles like the cutting dust as mentioned above. Therefore, the risk of floating particles preventing the entry of the fluid thereinto is eliminated.
In addition, as well known by a person skilled in art, a diameter of the pores as subjected to a mercury porosimeter measurement is being defined as the narrowest part within the series of open pores and corresponds with communication ports 3 in FIG. 1.